Ding Hui, Ke Zhonghe, Xiao Xiao, Xin Beibei, Xiong Hui, Lu Wen
Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, Shanghai, 200092, People's Republic of China.
Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Shanghai, 200092, People's Republic of China.
Int J Womens Health. 2025 Mar 13;17:739-749. doi: 10.2147/IJWH.S494703. eCollection 2025.
Cervical cancer is preceded by low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Human papillomavirus (HPV) test is a sensitive method for cervical cancer screening, but it is less specific compared with cytological examination, leading to overtreatment and reduced patient compliance. Therefore, new detection methods that can improve the accuracy of cervical cancer screening are needed.
In the present study, cervical exfoliated cell samples were collected from 228 Chinese individuals, including 114 healthy control individuals, 46 patients with LSIL, 21 patients with HSIL and 47 patients with cervical cancer. The DNA methylation levels of 12 cervical cancer-related genes were detected using quantitative multiplex methylation-specific PCR. All individuals were divided into high- or low-risk groups. Patients with HSIL and cervical cancer were assigned to the high-risk group, whereas healthy controls and patients with LSIL were assigned to the low-risk group. The ability to predict cancer risks was evaluated using ROC curves and a predictive model for cancer risk was constructed by linear regression analysis.
The methylation levels were significantly higher for all 12 genes in individuals with cervical cancer or HSIL, compared with those in LSIL or normal group. Family with sequence similarity 19 member A4 (), phosphatase and actin regulator 3 (), somatostatin (), Zic family member 1 (), paired box 1 () and zinc finger protein 671 () were used to construct a predictive model for cancer risk prediction, with a specificity of 89.6% and a sensitivity of 95.0%.
The present study demonstrated the methylation levels of 12 cervical cancer-related genes were higher in Chinese patients with HSIL or cervical cancer. Also, a predictive model was constructed to distinguish cervical cancer or HSCL from individuals with low risk.
宫颈癌之前会出现低级别鳞状上皮内病变（LSIL）和高级别鳞状上皮内病变（HSIL）。人乳头瘤病毒（HPV）检测是宫颈癌筛查的一种敏感方法，但与细胞学检查相比特异性较低，导致过度治疗并降低了患者的依从性。因此，需要能够提高宫颈癌筛查准确性的新检测方法。
在本研究中，从228名中国个体中收集宫颈脱落细胞样本，包括114名健康对照个体、46名LSIL患者、21名HSIL患者和47名宫颈癌患者。使用定量多重甲基化特异性PCR检测12个宫颈癌相关基因的DNA甲基化水平。所有个体被分为高风险或低风险组。HSIL和宫颈癌患者被归为高风险组，而健康对照和LSIL患者被归为低风险组。使用受试者工作特征曲线（ROC曲线）评估预测癌症风险的能力，并通过线性回归分析构建癌症风险预测模型。
与LSIL或正常组相比，宫颈癌或HSIL个体中所有12个基因的甲基化水平均显著更高。使用序列相似性家族19成员A4（）、磷酸酶和肌动蛋白调节剂3（）、生长抑素（）、锌指蛋白家族成员1（）、配对盒1（）和锌指蛋白671（）构建癌症风险预测模型，其特异性为89.6%，敏感性为95.0%。
本研究表明，中国HSIL或宫颈癌患者中12个宫颈癌相关基因的甲基化水平较高。此外，构建了一个预测模型，以将宫颈癌或HSCL与低风险个体区分开来。
